Methods and systems that monitor for an impending myocardial infarction

ABSTRACT

Implantable systems, and methods for use therewith, are provided for monitoring for an impending myocardial infarction. A signal indicative of changes in arterial blood volume is obtained. Such a signal can be a photoplethysmography signal or an impedance plethysmography signal. For each of a plurality of periods of time, a metric indicative of the areas under the curve of the signal or number of inflections in the signal is determined. An impending myocardial infarction is monitored for based on changes in the metric indicative of the area under the curve of the signal or number of inflections in the signal, and an alert and/or therapy is triggered in response to an impending myocardial infarction being predicted.

FIELD OF THE INVENTION

Embodiments of the present invention relate to implantable systems, andmethods for use therewith, for detecting, recognizing, and treating apatient before the occurrence of a myocardial infarction (MI).

BACKGROUND OF THE INVENTION

A myocardial infarction (MI or AMI for acute myocardial infraction),commonly known as a heart attack, occurs when the blood supply to partof the heart is interrupted. This is most commonly due to occlusion(blockage) of a coronary artery following the rupture of a vulnerableatherosclerotic plaque. This occurs through years of an undetected oruntreated combination of hypertension and abnormally high levels oflipids in a patient's blood. With time a patient builds up plaquedeposits in the interior lining of their coronary arteries. Thiscondition is commonly referred to as Coronary Artery Disease (CAD).

In some patients, these plaque deposits become severe enough that arestriction in coronary artery blood flow occurs and the patient becomessymptomatic. These restrictions can be clinically detected via variousdiagnostic and exercise tests. The patient begins to experience pain(angina) as well.

The typical treatment for this patient population is a PercutaneousCoronary Intervention (PCI), also known as Angioplasty. A balloon on theend of a catheter is inflated to remove the restricting plaque deposits,and then a stent is placed to stabilize the repaired region. In somecases, the restrictions are so extensive and severe that a CoronaryArtery Bypass Graft (CABG) procedure is required. If detected andtreated early enough, this patient group can avoid the deleteriouseffects resulting from a heart attack.

However, some patients are not as fortunate. These patients areasymptomatic. Their CAD remains undetected or untreated, and at a pointin time, a region of the plaque becomes vulnerable and a surface layerof inflammation develops. The inflamed region can rupture, expellingplaque material (calcified deposits) into the coronary artery. Plateletsin the blood stream recognize this foreign material and encapsulate it.A blood clot forms in close proximity or just downstream from theruptured region. This leads to a devastating chain of events for thepatient. The blockage in a coronary artery prevents the flow of bloodthat contains vital oxygen to the myocardial tissue supplied by thatcoronary artery. The patient begins to experience symptoms such asintense pain. Typical treatments are an immediate PCI procedure or animmediate transfusion of an anticoagulant or thrombolytic agent to breakor dissolve the blood clot. Time is of the essence. If not treatedimmediately, the affected myocardium will not receive sufficient oxygensupply and that region of cardiac muscle will literally die. This isreferred to as a Myocardial Infarction (MI), also known as a heartattack. If the patient survives, the MI can lead to furthercomplications with time, including a susceptibility to tachyarrhythmiasand a loss of heart function through the mechanisms of heart failure.The worst outcome is not surviving the heart attack. This can happenwhen the coronary artery blockage is so severe that the patientexperiences a lethal arrhythmia and can not be resuscitated.

The challenge is to detect, recognize, and successfully treat thepatient before a blockage of a coronary artery occurs. This is what theAmerican Heart Association (AHA) refers to as Acute Coronary Syndrome(ACS). This could be done in advance of the life threatening MI or thesubsequent tachyarrhythmias. Preventing the MI and protecting patientsfrom dangerous arrhythmias would be clinically important. It would savemany lives through prevention of a first heart attack, and could haveprofound implications in cost savings to our health care system. Many ofthe subsequent complications resulting from heart failure could beavoided as well.

SUMMARY OF THE INVENTION

Embodiments of the present invention are related to implantable systems,and methods for use therewith. Specific embodiments of the presentinvention relate to implantable systems that include an implantablesensor, and methods for use therewith.

Certain embodiments of the present invention relate to monitoring for animpending MI. In accordance with an embodiment, an implanted sensor isused to produce a signal that is indicative of changes in arterial bloodvolume. For a period of time a metric indicative of the area under thecurve of the signal is determined. The sensor can be implantedsubcutaneously in the pectoral region or it can be implanted elsewhere,such as the subcutaneous region of the abdomen. The signal indicative ofchanges in arterial blood volume can be a plethysmography signal such asa photo plethysmography signal or an impedance plethysmography signal.An impending MI is monitored for based on changes in the metricindicative of the area under the curve of the signal and an alert and/ortherapy can be triggered in response to an impending MI being detected.In accordance with an embodiment, the above can be repeated from time totime. In accordance with an embodiment, the signal that is indicative ofchanges in arterial blood volume can be an averaged signal that can beproduced by averaging a plurality of cardiac cycles of the signalobtained from the implanted sensor.

In accordance with an embodiment of the present invention, aplethysmography signal indicative of changes in arterial blood volume isproduced and a metric indicative of the area under the curve can bedetermined for a plurality of periods of time. In accordance with anembodiment, a baseline of the metric indicative of area under the curvecan be determined and an impending MI can be monitored for by comparingthe determined metric indicative of the area under the curve to thebaseline and predicting an impending MI if the determined metricindicative of the area under the curve falls below the baseline by atleast a specified threshold. In accordance with an embodiment,predicting an impending MI includes distinguishing between an impendingMI and a transient myocardial ischemic event based on a length of timethat the metric indicative of the area under the curve falls below thebaseline by at least the specified threshold. In accordance with anembodiment, an impending MI can be predicted if a decrease beyond aspecified threshold is detected, in the metric indicative of the areaunder the curve of the plethysmography signal, from one of the periodsof time to the immediately following one of the periods of time. In anembodiment, an impending MI can be predicted if a decrease by at least aspecified amount for at least a specified period of time is detected.

Certain embodiments of the present invention relate to monitoring for animpending MI by monitoring changes in vascular stiffness based onchanges in the area under the curve of a plethysmography signal. Animpending MI can be predicted if an increase in vascular stiffnessbeyond a specified threshold is detected, or if an increase in vascularstiffness beyond a specified threshold is detected within a specifiedtime period.

In accordance with an embodiment, the metric indicative of area underthe curve can be selected from a group consisting of an integral, awidth from the start to the end, and a full width at half maximum (FWHM)of a cycle of a signal indicative of changes in arterial blood volume.For each of the above, an average of the signal can be determined. Themetric indicative of area under the curve can then be measured based onthe average of the signal. In an embodiment of the present invention,the metric indicative of the area under the curve can be determined foreach of a plurality of cycles of the signal, and then an average ofthose metrics can be determined.

Other embodiments for monitoring for an impending MI include using achronically implanted device to produce a plethysmography signal that isindicative of changes in arterial blood volume. For each of a pluralityof periods of time, a metric indicative of a number of inflections canbe determined in the plethysmography signal for the period of time. Animpending MI can be monitored for based on changes in the metricindicative of the number of inflections in the plethysmography signal.An alert and/or therapy can be triggered in response to an impending MIbeing detected. In an embodiment, the number of inflection can bedetermined, e.g., by determining a first or second derivative of theplethysmography signal and counting a number of zero crossings during acycle of the plethysmography signal. This can be done after the signalis filtered, smoothed and/or averaged to get rid of inflections that aremerely due to noise. The metric indicative of inflections can be numberof peaks, number of positive peaks, or number of negative peaks in acycle of a plethysmography signal, or number of zero crossing in thefirst derivative of the plethysmography signal, but is not limitedthereto.

Certain embodiments of the present invention relate to monitoring for animpending MI with a chronically implanted device. A first signalindicative of changes in arterial blood volume can be obtained where thefirst signal can be, e.g., a photoplethysmography (PPG) signal or animpedance plethysmography (IPG) signal. A second signal indicative ofelectrical cardiac activity can also be obtained, where the secondsignal can be, e.g., an electrocardiogram (ECG) signal of anintracardiac electrogram (IEGM) signal. Based on the first and secondsignals, a metric indicative of aortic pulse wave velocity (PWV),diastolic blood pressure (DBP), heart rate (HR) and vascular stiffnesscan be determined. An impending MI can be monitored for based on themetrics indicative of PWV, DBP, HR and VS. An alert and/or therapy canbe triggered in response to an impending MI being detected. In anembodiment, the metric indicative of PWV can be a peak pulse arrivaltime (PAT), peripheral pulse arrival time (PPAT) or PWV determined as afunction of PAT or PPAT.

This description is not intended to be a complete description of, orlimit the scope of, the invention. Other features, aspects, and objectsof the various embodiments of the present invention can be obtained froma review of the specification, the figures, and the claims.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a high level flow diagram that is used to explain details formonitoring for an impending MI, in accordance with certain embodimentsof the present invention.

FIGS. 2A-2C includes exemplary PPG signal waveforms that are used toshow various metrics that are indicative of the area under the curve.

FIGS. 3A-3C includes exemplary IPG signal waveforms that are used toshow various metrics that are indicative of the area under the curve.

FIG. 4A is a flow diagram that is used to explain details of one of thesteps (i.e., step 106) of the flow diagram of FIG. 1, according to anembodiment of the invention.

FIG. 4B is a flow diagram that is used to explain details of one of thesteps (i.e., step 404) of the flow diagram of FIG. 4A, according to anembodiment of the invention.

FIG. 4C is a flow diagram that is used to explain further details of oneof the steps (i.e., step 106) of the flow diagram of FIG. 1, accordingto an alternate embodiment of the invention.

FIG. 5A is a flow diagram that is used to explain details for monitoringfor an impending MI based on a number of inflections in aplethysmography signal.

FIG. 5B is a flow diagram that is used to explain details of one of thesteps (i.e., step 506) of the flow diagram of FIG. 5A, according to anembodiment of the invention.

FIG. 6 is a flow diagram that is used to explain details for monitoringfor an impending MI, in accordance with certain embodiments of thepresent invention.

FIG. 7A illustrates an exemplary implantable stimulation device that canbe used to perform various embodiments of the present invention.

FIGS. 7B and 7C illustrate exemplary implantable monitoring devices thatcan be used to perform various embodiments of the present invention.

FIG. 8 is a simplified block diagram that illustrates possiblecomponents of the implantable devices shown in FIGS. 7A-7C.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of the best modes presently contemplatedfor practicing various embodiments of the present invention. Thedescription is not to be taken in a limiting sense but is made merelyfor the purpose of describing the general principles of the invention.The scope of the invention should be ascertained with reference to theclaims. In the description of the invention that follows, like numeralsor reference designators will be used to refer to like steps, parts orelements throughout. In addition, the first digit of a reference numberidentifies the drawing in which the reference number first appears.

It would be apparent to one of skill in the art reading this descriptionthat the various embodiments of the present invention, as describedbelow, may be implemented in many different embodiments of hardware,software, firmware, and/or the entities illustrated in the figures. Anyactual software, firmware and/or hardware described herein is notlimiting of the present invention. Thus, the operation and behavior ofthe embodiments of the present invention will be described with theunderstanding that modifications and variations of the embodiments arepossible, given the level of detail presented herein.

Various embodiments of the present invention for predicting an impendingMI will now be summarized beginning with a description of the high levelflow diagrams of FIG. 1. Where embodiments of the present invention aresummarized with reference to the high level flow diagrams, variousalgorithmic steps are summarized in individual ‘blocks’. Such blocksdescribe specific actions or decisions that are made or carried out asthe algorithm proceeds. Where a microcontroller (or equivalent) isemployed, the flow diagrams presented herein provides the basis for a‘control program’ that may be used by such a microcontroller (orequivalent) to effectuate the desired control of the implantable system.Those skilled in the art may readily write such a control program basedon the flow diagram and other description presented herein. Embodimentsof the present invention are not limited to the exact order and/orboundaries of the steps shown in the flow diagrams. In fact, many of thesteps can be performed in a different order than shown, and many stepscan be combined, or separated into multiple steps. All such variationsare encompassed by the present invention. The only time order isimportant is where a step acts on the result of a previous step.

Referring to FIG. 1, at step 102, a plethysmography signal indicative ofchanges in arterial blood volume is obtained using an implantedextravascular sensor. For certain embodiments it is preferred that aplurality of cardiac cycles of the obtained plethysmography signal areaveraged to produce a plethysmography signal that is an averagedplethysmography signal. At step 104 a metric indicative of the areaunder the curve of the plethysmography signal is determined for each ofa plurality of periods of time. At step 106, based on changes in ametric indicative of the area under the curve of the plethysmographysignal, an impending myocardial infarction is monitored for. In anembodiment of the present invention, monitoring for an impending MIincludes distinguishing between an impending MI and a transientmyocardial ischemic event, as will be explained below. At step 108, analert and/or therapy can be triggered in response to an impending MIbeing detected.

As indicated by arrowed line 110, steps 102-106 are repeated from timeto time, e.g., periodically, or in response to a triggering event. Forexample, steps 102-106 can be performed substantially continually, orperiodically (e.g., once an hour, a day, a week, or the like).Additionally, steps 102-106 can be performed aperiodically, e.g., inresponse to a triggering event, many examples of which are discussedbelow.

In an embodiment of the present invention, the plethysmography signalindicative of changes in arterial blood volume can be aphotoplethysmography (PPG) signal. Volume changes in blood vessels occurin a pulsatile manner with each beat of the heart as blood flows in andout of a portion of the body. A PPG sensor produces waveformmeasurements reflecting changes in arterial blood volume. Thesewaveforms measurements are similar to arterial pressure waveformmeasurements because changes in arterial pressure correspond to relativechanges in arterial blood volume. A metric indicative of the area underthe curve of the PPG signal can be determined for each of a plurality ofperiods of time. For certain embodiments it is preferred that aplurality of cardiac cycles of the obtained PPG signal are averaged toproduce a PPG waveform that is an averaged PPG waveform.

Exemplary PPG sensors are discussed below with reference to FIGS. 7A-7C.The PPG sensor can be implanted, e.g., in the pectoral region of apatient. Thus, it is practical that the PPG sensor can be integratedwith or attached to the housing of a pacemaker or implantablecardioverter-defibrillator (ICD), as can be appreciated from FIGS. 7Aand 8 discussed below. Alternative locations for implantation of the PPGsensor include, but are not limited to, the patient's abdomen.

In accordance with an embodiment of the present invention, theplethysmography signal indicative of changes in arterial blood volumecan be an implanted impedance plethysmography (IPG) signal. An impedanceplethysmography sensor can measure the change in arterial blood volume(venous blood volume as well as the pulsation of the arteries) for aspecific body segment. As the arterial blood volume changes, theelectrical impedance (resistance) also changes. A metric indicative ofthe area under the curve of the IPG signal is determined for each of aplurality of periods of time. For certain embodiments it is preferredthat a plurality of cardiac cycles of the obtained IPG signal areaveraged to produce an IPG signal that is an averaged IPG signal.

The IPG sensor can be implanted, e.g., in the pectoral region of apatient. Thus, it is practical that the IPG sensor can be integratedwith or attached to the housing or a pacemaker or ICD, as can beappreciated from FIGS. 7A and 8 discussed below. Alternative locationsfor implantation of the IPG sensor include, but are not limited to, thepatient's abdomen.

FIG. 2A illustrates an exemplary PPG signal waveform 202 that is used toshow various metrics indicative of area under the curve. The peak topeak amplitude of the PPG signal is designated as A1. The time from therise of the PPG waveform to the dichrotic notch is designated as t₁. Asshown in FIG. 2A, a metric indicative of area under signal 202 can be anintegral 204 of at least one cycle (t2) of the plethysmography signalwaveform. In an embodiment, the area can be determined by multiplyingthe amplitude of the PPG signal by the time from the rise of the PPGwaveform to the dichrotic notch (t₁). This calculation can be normalizedwith time or a running aggregate area can be calculated.

As shown in FIG. 2B, the metric indicative of area under curve 202 canalso be a width 206 of a cycle of signal 202 where the width is measuredfrom the start to the end of a cycle of a PPG signal. Additionally, asshown in FIG. 2C, a metric indicative of area under curve 202 can be afull width at half maximum (FWHM) 208 of a cycle of the PPG signal.

In accordance with an embodiment of the present invention, changes inthe PPG waveform during a rupture of a region plaque within a coronaryartery can be detected by using the area under the curve. For example,if the overall heart rate increases above a heart rate threshold, e.g.,120 beats per minute, and there is a significant reduction in the areaunder the PPG curve, then an acute event such as plaque rupture could bein process. In an embodiment of the present invention, the threshold canbe a fixed threshold or a percentage, e.g., 150% or 175% of thepatient's baseline heart rate.

FIG. 3A illustrates an exemplary IPG signal waveform that is used toshow various metrics indicative of area under the curve. As shown inFIG. 3A, a metric indicative of area under signal 302 can be an integral304 of at least one cycle of the IPG signal. As an example, one cyclecan be t₁ as shown in FIG. 3A. As shown in FIG. 3B, the metricindicative of area under curve 302 can also be a width 306 of a cycle ofthe signal 302, where the width is measured from the start to end of acycle of an IPG signal. Additionally, as shown in FIG. 3C, a metricindicative of area under curve 302 can be a full width at half maximum308 of the IPG signal.

FIG. 4A is a flow diagram that is used to explain details of one of thesteps (i.e., step 106) of the flow diagram of FIG. 1, according to anembodiment of the invention. At step 402 the metrics indicative of thearea under the curve are compared to a baseline. The baseline can bedetermined by monitoring for the metric indicative of the area under thecurve when a patient is not experiencing an MI. If the determined metricindicative of the area under the curve falls below the baseline by atleast a specified threshold, an impending MI can be predicted. As anexample, the specified threshold can be a percentage of the baseline ora predetermined value, but is not limited thereto.

FIG. 4B is a flow diagram that is used to explain details of one of thesteps (i.e., step 404) of the flow diagram of FIG. 4A, according to anembodiment of the invention. At step 406 an impending MI and a transientmyocardial ischemic event are distinguished between based on a length oftime that the metric indicative of the area under the curve falls belowthe baseline by at least a specified threshold. The length of time canbe, for example, set at a level (e.g., 15 minutes or some other definedperiod of time) that will help distinguish a transient ischemic eventfrom an impending MI. In an embodiment of the invention, it can beexpected that an ischemic event will result in a reduction in area underthe curve for a relatively shorter period of time as compared to animpending MI. In an embodiment of the present invention, an impending MIis predicted if the metric indicative of the area under the curve of theplethysmography signal decreases by at least a specified amount for atleast a specified period of time (e.g., by at least 30 percent, for atleast 30 minutes). Otherwise, the detected event that caused thedecrease in the area under the curve of the plethysmography signal isclassified as a transient ischemic event.

FIG. 4C is a flow diagram that is used to explain further details of oneof the steps (i.e., step 106) of the flow diagram of FIG. 1, accordingto an alternate embodiment of the invention. At step 408 a change invascular stiffness is detected based on changes in the area under thecurve of the plethysmography signal. For example, a reduction in thearea under the curve can result in an increase in vascular stiffness. Atstep 410 an impending MI is monitored for based on changes in vascularstiffness that are based on changes in the area under the curve of theplethysmography signal. In an embodiment of the invention, an impendingMI is predicted if an increase in vascular stiffness is detected beyonda specified threshold and/or if an increase in vascular stiffness beyonda specified threshold is detected within a specified time period.

FIG. 5A is a flow diagram that is used to explain details for monitoringfor an impending MI based on a number of inflections in aplethysmography signal. In step 102 a plethysmography signal is producedthat is indicative of changes in arterial blood volume by using animplanted sensor. In step 504 a metric indicative of a number ofinflections in the plethysmography signal is determined for each of aplurality of periods of time. In step 506 an impending MI is monitoredfor based on changes in the metric indicative of the number ofinflections in the plethysmography signal. In step 108 an alert and/ortherapy is triggered in response to an impending MI being detected.

The technique described with reference to FIG. 5 can be performed by achronically implanted device, examples of which are discussed below. Thedevice can use an implanted sensor to produce the plethysmography signalthat is indicative of changes in arterial blood volume. For each of aplurality of periods of time, the device can determine a metricindicative of a number of inflections in the plethysmography signal forthe period of time. The metric indicative of inflections can be, e.g.,number of peaks, number of positive peaks, or number of negative peaksin a cycle of a plethysmography signal. The number of inflections can bedetermined, for example, by determining a first or second derivative ofthe plethysmography signal and counting a number of zero crossingsduring a cycle of the plethysmography signal. In a specific embodiment,the number of inflections can be determined after the signal isfiltered, smoothed, and/or averaged to get rid of inflections that aremerely due to noise.

FIG. 5B is a flow diagram that is used to explain details of one of thesteps (i.e., step 506) of the flow diagram of FIG. 5A, according to anembodiment of the invention. In step 508 an impending MI can bemonitored for based on changes in the metric indicative of the number ofinflections in the plethysmography signal once a metric indicative of anumber of inflections in the plethysmography signal has been determined.For example, an impending MI can be detected by determining a baselineof the metric indicative of the number of inflections in theplethysmography signal when a patient is not experiencing an MI andthereafter comparing the determined metric indicative of the number ofinflections to the baseline. In step 510 an impending MI can bepredicted if the determined metric indicative of the number ofinflections increases beyond the baseline by at least a specifiedthreshold.

In certain embodiments, detecting an impending MI can also includedistinguishing between an impending MI and a transient myocardialischemic event based on a length of time that the metric indicative ofthe number of inflections remains increased beyond the baseline by atleast the specified threshold. Because it is expected that an ischemicevent will result in an increase in the number of inflections for only arelatively short period of time, the length of time is set at a levelthat will help distinguish an ischemic event from an impending MI.

In accordance with an embodiment of the present invention, an impendingMI is predicted if an increase beyond a specified threshold is detected,in the metric indicative of the number of inflections in theplethysmography signal, from one of the periods of time to theimmediately following one of the periods of time. In an embodiment ofthe invention, an impending MI can be predicted if the metric indicativeof the number of inflections in the plethysmography signal increases byat least a specified amount for at least a specified period of time. Forexample, an impending MI can be predicted if the metric indicative ofthe number of inflections in the plethysmography signal increases by atleast 30 percent, for at least 15 minutes, or some other definedpercentage or period of time. The above percentage and time suggestionsare exemplary and are not made to be taken as limiting.

Certain embodiments of the present invention relate to an implantablesystem configured to monitor for an impending MI. The system includes animplantable sensor to produce a plethysmography signal that isindicative of changes in arterial blood volume. A monitor can beconfigured to determine a metric indicative of the area under the curveof the plethysmography signal for each of a plurality of periods oftime. The monitor can also be configured to monitor for an impending MIbased on changes in the metric indicative of the area under the curve ofthe plethysmography signal. In an embodiment of the present invention,the monitor can be configured to determine a metric indicative of anumber of inflections in the plethysmography signal for each of aplurality of the periods of time and monitor for an impending MI basedon changes in the metric indicative of the number of inflections in theplethysmography signal.

In an embodiment of the present invention, the monitor can be configuredto monitor for an impending MI, based of changes in the metricindicative of the area under the curve of the plethysmography signal, bycomparing the determined metrics indicative of the area under the curveto a baseline, and predicting an impending MI if the determined metricindicative of the area under the curve falls below the baseline by atleast a specified threshold. In an embodiment of the invention, thethreshold can be set at a level that will help distinguish an ischemicevent from an impending MI, because it is expected that an ischemicevent will result in a relatively smaller reduction in area under thecurve.

In an embodiment of the present invention, the monitor can be configuredto monitor for an impending MI, based on changes in the metricindicative of the number of inflections in the plethysmography signal,by comparing the determined metrics indicative of the number ofinflections to a baseline, and predicting an impending MI if thedetermined metric indicative of the number of inflections increasesabove the baseline by at least a specified threshold.

FIG. 6 is a flow diagram that is used to explain details for monitoringfor an impending MI, in accordance with certain embodiments of thepresent invention. At step 602 a first signal indicative of changes inarterial blood volume is obtained, where the first signal can be, e.g.,a photoplethysmography (PPG) signal or an impedance plethysmography(IPG) signal. At step 604 a second signal indicative of electricalcardiac activity is obtained, where the second signal can be, e.g., anelectrocardiogram (ECG) signal or an intracardiac electrogram (IEGM)signal. At step 606, based on the first and second signals, a metricindicative of aortic pulse wave velocity (PWV), diastolic blood pressure(DBP), heart rate (HR) and vascular stiffness can be determined.

In an embodiment of the invention, Pulse Wave Velocity (PWV) can be anindicator of vascular stiffness. The PWV measurement is the velocity ofthe pulse wave between two points as measured by two transducers locatedat reference points outside of the arterial system. This is typicallymeasured at the Aorta. PWV is strongly associated with the presence andextent of atherosclerosis and constitutes a forceful marker andpredictor of cardiovascular risk. In an embodiment, the number of peaksin the plethysmography signal can be used as surrogates of vascularstiffness. For example, the higher the number of peaks per cardiacsignal, the stiffer the vasculature.

In an embodiment of the present invention, the metric indicative of PWVcan be a Pulse Arrival Time (PAT), PPAT, or PWV determined as a functionof PAT or PPAT, while the metric indicative of vascular stiffness can bea measure of the area under the curve of the first signal or the numberof inflections in the first signal, but is not limited thereto. U.S.patent application Ser. No. 11/848,586, entitled “IMPLANTABLE SYSTEMICBLOOD PRESSURE MEASUREMENT SYSTEMS AND METHODS” (Fayram et al.), filedon Aug. 31, 2007, which is incorporated herein by reference, providesexemplary details of how metrics indicative of PWV and DBP can bedetermined on the first and second signals.

At steps 608-612, based on the first signal and/or second signal,metrics indicative of diastolic blood pressure (DBP), heart rate (HR),and vascular stiffness (VS) can be determined. At step 614 an impendingMI can be monitored for based on the metrics indicative of PWV, DBP, HRand VS. At step 616 an alert (e.g., patient alert 819 in FIG. 8) and/ortherapy can be triggered in response to an impending MI being detected.

In the event of an impending MI, it is believed that PWV, DBP, VS and HRshould all increase. Thus, when an increase in each of PWV, DBP, VS andHR beyond a corresponding threshold is detected, an alert and/or therapycan be triggered signaling an impending MI. In an embodiment, animpending MI can be detected if a majority of the metrics indicative ofPWV, DBP, HR and VS exceed there corresponding threshold.

Exemplary Implantable System

FIGS. 7A-7C and 8 will now be used to describe exemplary implantablesystems that can be used to monitor for an impending MI, in accordancewith embodiments of the present invention. Referring to FIG. 7A, theimplantable system is shown as including an implantable stimulationdevice 710, which can be a pacing device and/or an implantablecardioverter defibrillator. The device 710 is shown as being inelectrical communication with a patient's heart 712 by way of threeleads, 720, 724 and 730, which can be suitable for deliveringmulti-chamber stimulation and shock therapy. The leads can also be usedto obtain IEGM signals, for use in embodiments of the present invention.Instead of having leads with electrodes attached to the heart, it isalso possible that subcutaneous electrodes can be used to obtain ECGsignals. In still other embodiments, it's possible that the electrodesare located on the housing of the implantable device 710, and that suchelectrodes are used to obtain subcutaneous ECG signals. In this latterembodiment, the device 710 may not be capable of pacing and/ordefibrillation, but rather, the implantable device 710 can be primarilyfor monitoring purposes.

The implantable system is also shown as including an implantablephotoplethysmography (PPG) sensor 703 that can be used to produce a PPGsignal, similar to signal 202 shown in FIGS. 2A-2C. Referring to FIGS.7A, the PPG 703 sensor includes a light source 705 and a light detector707. The light source 705 can include, e.g., at least one light-emittingdiode (LED), incandescent lamp or laser diode. The light detector 707can include, e.g., at least one photoresistor, photodiode,phototransistor, photodarlington or avalanche photodiode. Lightdetectors are often also referred to as photodetectors or photocells.

The light source 705 outputs light that is reflected or backscaftered bysurrounding patient tissue, and reflected/backscattered light isreceived by the light detector 707. In this manner, changes in reflectedlight intensity are detected by the light detector, which outputs asignal indicative of the changes in detected light. The output of thelight detector can be filtered and amplified. The signal can also beconverted to a digital signal using an analog to digital converter, ifthe PPG signal is to be analyzed in the digital domain. Additionaldetails of exemplary implantable PPG sensors are disclosed in U.S. Pat.Nos. 6,409,675 and 6,491,639, both entitled “Extravascular HemodynamicSensor” (both Turcott), which are incorporated herein by reference.

A PPG sensor can use a single wavelength of light, or a broad spectrumof many wavelengths. In the alternate embodiments, the light source canbe any source of radiant energy, including laser diode, heated filament,and ultrasound transducer. The detector can be any detector of radiantenergy, including phototransistor, photodetector, ultrasound transducer,piezoelectric material, and thermoelectric material.

It is generally the output of the photodetector that is used to producea PPG signal. However, there exist techniques where the output of thephotodetector is maintained relatively constant by modulating the drivesignal used to drive the light source, in which case the PPG signal isproduced using the drive signal, as explained in U.S. Pat. No.6,731,967, entitled “Methods and Devices for Vascular Plethysmographyvia Modulation of Source Intensity,” (Turcott), which is incorporatedherein by reference.

The PPG sensor 703 can be attached to a housing 740 of an implantabledevice, which as mentioned above can be, e.g., a pacemaker and/or animplantable cardioverter-defibrillator (ICD), or a simple monitoringdevice. Exemplary details of how to attach a sensor module to animplantable cardiac stimulation device are described in U.S. patentapplication Ser. No. 10/913,942, entitled “Autonomous Sensor Modules forPatient Monitoring” (Turcott et al.), filed Aug. 4, 2004, (which isincorporated herein by reference. It is also possible that the PPGsensor 703 be integrally part of the implantable cardiac stimulationdevice 710. For example, the PPG sensor 703 can be located within thehousing 740 of an ICD (or pacemaker) that has a window through whichlight can be transmitted and detected. In a specific embodiment, the PPGsensor 703 has a titanium frame with a light transparent quartz windowthat can be welded into a corresponding slot cut in the housing of theICD. This will insure that the ICD enclosure with the welded PPG sensorwill maintain a hermetic condition. In alternative embodiments, the PPGsensor can be remote from housing 740 and can communicate withcomponents within the housing via a bus (e.g., including one or morewires), or wirelessly, but is not limited thereto.

Where the PPG sensor 703 is incorporated into or attached to achronically implantable device 710, the light source 705 and the lightdetector 707 can be mounted adjacent to one another on the housing orheader of the implantable device. The light source 705 and the lightdetector 707 are preferably placed on the side of the implantable device710 that, following implantation, faces the chest wall, and areconfigured such that light cannot pass directly from the source to thedetector. The placement on the side of the device 710 that faces thechest wall maximizes the signal to noise ratio by directing the signaltoward the highly vascularized musculature, and shielding the source anddetector from ambient light that enters the body through the skin.Alternatively, at the risk of increasing susceptibility to ambientlight, the light source 705 and the light detector 707 can be placed onthe face of the device 710 that faces the skin of the patient.

The implantable PPG sensor 703 outputs a PPG signal similar to signal202 shown in FIGS. 2A-2C. More specifically, the output of the lightdetector 705 can be an analog signal that resembles signal 202. Such asignal can be filtered and/or amplified as appropriate, e.g., to removerespiratory affects on the signal, and the like. Additionally, thesignal can be digitized using an analog to digital converter. Based onthe PPG signal (and in some embodiments an ECG or IEGM obtained usingimplanted electrodes) metrics indicative of area under the curve, numberof inflections, vascular stiffness, PWV, DBP and/or HR can bedetermined, in accordance with embodiments of the present invention.

Still referring to FIG. 7A, to sense atrial cardiac signals and toprovide right atrial chamber stimulation therapy, the device 710 iscoupled to an implantable right atrial lead 720 having at least anatrial tip electrode 722, which typically is implanted in the patient'sright atrial appendage. To sense left atrial and ventricular cardiacsignals and to provide left-chamber pacing therapy, the device 710 iscoupled to a “coronary sinus” lead 724 designed for placement in the“coronary sinus region” via the coronary sinus for positioning a distalelectrode adjacent to the left ventricle and/or additional electrode(s)adjacent to the left atrium. As used herein, the phrase “coronary sinusregion” refers to the vasculature of the left ventricle, including anyportion of the coronary sinus, great cardiac vein, left marginal vein,left posterior ventricular vein, middle cardiac vein, and/or smallcardiac vein or any other cardiac vein accessible by the coronary sinus.

Accordingly, an exemplary coronary sinus lead 724 is designed to receiveatrial and ventricular cardiac signals and to deliver left ventricularpacing therapy using at least a left ventricular tip electrode 726, leftatrial pacing therapy using at least a left atrial ring electrode 727,and shocking therapy using at least a left atrial coil electrode 728.

The device 710 is also shown in electrical communication with thepatient's heart 712 by way of an implantable right ventricular lead 730having, in this embodiment, a right ventricular tip electrode 732, aright ventricular ring electrode 734, a right ventricular (RV) coilelectrode 736, and an SVC coil electrode 738. Typically, the rightventricular lead 730 is transvenously inserted into the heart 712 so asto place the right ventricular tip electrode 732 in the rightventricular apex so that the RV coil electrode 736 will be positioned inthe right ventricle and the SVC coil electrode 738 will be positioned inthe superior vena cava. Accordingly, the right ventricular lead 730 iscapable of receiving cardiac signals and delivering stimulation in theform of pacing and shock therapy to the right ventricle.

FIG. 7B illustrates an alternative embodiment of the implantable device710. Here the housing 740 of the device is shown as small, thin, andoblong, with smooth surfaces and a physiologic contour which minimizestissue trauma and inflammation. The oblong geometry of the housing 740is desirable because it maximizes separation of electrodes 742 andprevents rotation of the monitor within the tissue pocket, therebyallowing interpretation of morphology features in an ECG sensed usingelectrodes 742. Two ECG electrodes 742 are shown, however more can bepresent. In the alternate embodiment illustrated in FIGS. 7C, three ECGelectrodes 742 are present, one at each apex of the triangle formed bythe device housing 740. These three electrodes allow the three standardsurface ECG leads I-III to be approximated. In an embodiment, four ormore ECG electrodes might be used, with each orthogonal electrode pairproviding orthogonal ECG signals. Alternatively, an embodiment lackingECG electrodes is possible. A further alternative has a single ECGelectrode with the monitor housing acting as the other electrode in thepair. U.S. Pat. No. 6,409,675, which was incorporated above byreference, provides some additional details of an implantable monitorthat includes ECG electrodes on its housing and a PPG sensor. FIGS. 7Band 7C show that the implantable device 710 also include a PPG sensor703.

FIG. 8 will now be used to provide some exemplary details of thecomponents of the implantable devices 710. Referring now to FIG. 8, eachof the above implantable devices 710, and alternative versions thereof,can include a microcontroller 860. As is well known in the art, themicrocontroller 860 typically includes a microprocessor, or equivalentcontrol circuitry, and can further include RAM or ROM memory, logic andtiming circuitry, state machine circuitry, and I/O circuitry. Typically,the microcontroller 860 includes the ability to process or monitor inputsignals (data) as controlled by a program code stored in a designatedblock of memory. The details of the design of the microcontroller 860are not critical to the present invention. Rather, any suitablemicrocontroller 860 can be used to carry out the functions describedherein. The use of microprocessor-based control circuits for performingtiming and data analysis functions are well known in the art. Inspecific embodiments of the present invention, the microcontroller 860performs some or all of the steps associated with monitoring for animpending MI. Additionally, the microcontroller 860 may detectarrhythmias, and select and control delivery of anti-arrhythmia therapy.

Representative types of control circuitry that may be used with theinvention include the microprocessor-based control system of U.S. Pat.No. 4,940,052 (Mann et. al.) and the state-machines of U.S. Pat. No.4,712,555 (Sholder) and U.S. Pat. No. 4,944,298 (Sholder). For a moredetailed description of the various timing intervals used within thepacing device and their inter-relationship, see U.S. Pat. No. 4,788,980(Mann et. al.). The '052, '555, '298 and '980 patents are incorporatedherein by reference.

Depending on implementation, the device 710 can be capable of treatingboth fast and slow arrhythmias with stimulation therapy, includingpacing, cardioversion and defibrillation stimulation. While a particularmulti-chamber device is shown, this is for illustration purposes only,and one of skill in the art could readily duplicate, eliminate ordisable the appropriate circuitry in any desired combination to providea device capable of treating the appropriate chamber(s) with pacing,cardioversion and defibrillation stimulation. For example, where theimplantable device is a monitor that does not provide any therapy, it isclear that many of the blocks shown may be eliminated.

The housing 740, shown schematically in FIG. 8, is often referred to asthe “can”, “case” or “case electrode” and may be programmably selectedto act as the return electrode for all “unipolar” modes. The housing 740may further be used as a return electrode alone or in combination withone or more of the coil electrodes, 728, 736 and 738, for shockingpurposes. The housing 740 can further include a connector (not shown)having a plurality of terminals, 842, 844, 846, 848, 852, 854, 856, and858 (shown schematically and, for convenience, the names of theelectrodes to which they are connected are shown next to the terminals).As such, to achieve right atrial sensing and pacing, the connectorincludes at least a right atrial tip terminal (A_(R) TIP) 842 adaptedfor connection to the atrial tip electrode 722.

To achieve left atrial and ventricular sensing, pacing and shocking, theconnector includes at least a left ventricular tip terminal (V_(L) TIP)844, a left atrial ring terminal (A_(L) RING) 846, and a left atrialshocking terminal (A_(L) COIL) 848, which are adapted for connection tothe left ventricular ring electrode 726, the left atrial tip electrode727, and the left atrial coil electrode 728, respectively.

To support right ventricle sensing, pacing and shocking, the connectorfurther includes a right ventricular tip terminal (V_(R) TIP) 852, aright ventricular ring terminal (V_(R) RING) 854, a right ventricularshocking terminal (R_(V) COIL) 856, and an SVC shocking terminal (SVCCOIL) 858, which are adapted for connection to the right ventricular tipelectrode 732, right ventricular ring electrode 734, the RV coilelectrode 726, and the SVC coil electrode 738, respectively.

An atrial pulse generator 870 and a ventricular pulse generator 872generate pacing stimulation pulses for delivery by the right atrial lead720, the right ventricular lead 730, and/or the coronary sinus lead 724via an electrode configuration switch 874. It is understood that inorder to provide stimulation therapy in each of the four chambers of theheart, the atrial and ventricular pulse generators, 870 and 872, mayinclude dedicated, independent pulse generators, multiplexed pulsegenerators, or shared pulse generators. The pulse generators, 870 and872, are controlled by the microcontroller 860 via appropriate controlsignals, 876 and 878, respectively, to trigger or inhibit thestimulation pulses.

The microcontroller 860 further includes timing control circuitry 879which is used to control pacing parameters (e.g., the timing ofstimulation pulses) as well as to keep track of the timing of refractoryperiods, noise detection windows, evoked response windows, alertintervals, marker channel timing, etc., which is well known in the art.Examples of pacing parameters include, but are not limited to,atrio-ventricular delay, interventricular delay and interatrial delay.

The switch bank 874 includes a plurality of switches for connecting thedesired electrodes to the appropriate I/O circuits, thereby providingcomplete electrode programmability. Accordingly, the switch 874, inresponse to a control signal 880 from the microcontroller 860,determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, etc.) by selectively closing the appropriate combination ofswitches (not shown) as is known in the art.

Atrial sensing circuits 882 and ventricular sensing circuits 884 mayalso be selectively coupled to the right atrial lead 720, coronary sinuslead 724, and the right ventricular lead 730, through the switch 874 fordetecting the presence of cardiac activity in each of the four chambersof the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR.SENSE) sensing circuits, 882 and 884, may include dedicated senseamplifiers, multiplexed amplifiers, or shared amplifiers. The switch 874determines the “sensing polarity” of the cardiac signal by selectivelyclosing the appropriate switches, as is also known in the art. In thisway, the clinician may program the sensing polarity independent of thestimulation polarity.

Each sensing circuit, 882 and 884, preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables the device 710 to deal effectively withthe difficult problem of sensing the low amplitude signalcharacteristics of atrial or ventricular fibrillation. Such sensingcircuits, 882 and 884, can be used to determine cardiac performancevalues used in the present invention. Alternatively, an automaticsensitivity control circuit may be used to effectively deal with signalsof varying amplitude.

The outputs of the atrial and ventricular sensing circuits, 882 and 884,are connected to the microcontroller 860 which, in turn, are able totrigger or inhibit the atrial and ventricular pulse generators, 870 and872, respectively, in a demand fashion in response to the absence orpresence of cardiac activity, in the appropriate chambers of the heart.The sensing circuits, 882 and 884, in turn, receive control signals oversignal lines, 886 and 888, from the microcontroller 860 for purposes ofmeasuring cardiac performance at appropriate times, and for controllingthe gain, threshold, polarization charge removal circuitry (not shown),and timing of any blocking circuitry (not shown) coupled to the inputsof the sensing circuits, 882 and 886.

For arrhythmia detection, the device 710 includes an arrhythmia detector862 that utilizes the atrial and ventricular sensing circuits, 882 and884, to sense cardiac signals to determine whether a rhythm isphysiologic or pathologic. The timing intervals between sensed events(e.g., P-waves, R-waves, and depolarization signals associated withfibrillation) can be classified by the microcontroller 860 by comparingthem to a predefined rate zone limit (i.e., bradycardia, normal, lowrate VT, high rate VT, and fibrillation rate zones) and various othercharacteristics (e.g., sudden onset, stability, physiologic sensors, andmorphology, etc.) in order to assist with determining the type ofremedial therapy that is needed (e.g., bradycardia pacing,anti-tachycardia pacing, cardioversion shocks or defibrillation shocks,collectively referred to as “tiered therapy”). Additionally, thearrhythmia detector 862 can perform arrhythmia discrimination, e.g.,using measures of arterial blood pressure determined in accordance withembodiments of the present invention. Exemplary details of sucharrhythmia discrimination, including tachyarrhythmia classification, arediscussed above. The arrhythmia detector 862 can be implemented withinthe microcontroller 860, as shown in FIG. 8. Thus, this detector 862 canbe implemented by software, firmware, or combinations thereof. It isalso possible that all, or portions, of the arrhythmia detector 862 canbe implemented using hardware. Further, it is also possible that all, orportions, of the arrhythmia detector 862 can be implemented separatefrom the microcontroller 860.

In accordance with embodiments of the present invention, the implantabledevice 710 includes a MI monitor 867, which can monitor for an impendingMI using the techniques described above with reference to FIGS. 1-6. TheMI monitor 867 can be implemented within the microcontroller 860, asshown in FIG. 8, and can be implemented by software, firmware, orcombinations thereof. It is also possible that all, or portions, of theMI monitor 867 to be implemented using hardware. Further, it is alsopossible that all, or portions, of the MI monitor 867 to be implementedseparate from the microcontroller 860. The MI monitor 867 can be used ina closed loop control system to detect, recognize and treat a patientbefore a blockage of a coronary artery occurs.

The implantable device 710 can also include a pacing controller 866,which can adjust a pacing rate and/or pacing intervals based on measuresof arterial blood pressure, in accordance with embodiments of thepresent invention. The pacing controller 866 can be implemented withinthe microcontroller 860, as shown in FIG. 8. Thus, the pacing controller866 can be implemented by software, firmware, or combinations thereof.It is also possible that all, or portions, of the pacing controller 866can be implemented using hardware. Further, it is also possible thatall, or portions, of the pacing controller 866 can be implementedseparate from the microcontroller 860.

The implantable device can also include a medication pump 803, which candeliver medication to a patient if an impending MI is detected.Information regarding implantable medication pumps may be found in U.S.Pat. No. 4,731,051 (Fischell) and in U.S. Pat. No. 4,947,845 (Davis),both of which are incorporated by reference herein.

Still referring to FIG. 8, cardiac signals are also applied to theinputs of an analog-to-digital (A/D) data acquisition system 890. Thedata acquisition system 890 is configured to acquire IEGM and/or ECGsignals, convert the raw analog data into a digital signal, and storethe digital signals for later processing and/or telemetric transmissionto an external device 802. The data acquisition system 890 can becoupled to the right atrial lead 720, the coronary sinus lead 724, andthe right ventricular lead 730 through the switch 874 to sample cardiacsignals across any pair of desired electrodes. In specific embodiments,the data acquisition system 890 may be used to acquire IEGM signals forthe analysis of changes in the ST-segment for detecting myocardialischemia, and for monitoring PWV, DBP and HR.

The data acquisition system 890 can be coupled to the microcontroller860, or other detection circuitry, for detecting an evoked response fromthe heart 712 in response to an applied stimulus, thereby aiding in thedetection of “capture”. Capture occurs when an electrical stimulusapplied to the heart is of sufficient energy to depolarize the cardiactissue, thereby causing the heart muscle to contract. Themicrocontroller 860 detects a depolarization signal during a windowfollowing a stimulation pulse, the presence of which indicates thatcapture has occurred. The microcontroller 860 enables capture detectionby triggering the ventricular pulse generator 872 to generate astimulation pulse, starting a capture detection window using the timingcontrol circuitry 879 within the microcontroller 860, and enabling thedata acquisition system 890 via control signal 892 to sample the cardiacsignal that falls in the capture detection window and, based on theamplitude, determines if capture has occurred.

The implementation of capture detection circuitry and algorithms arewell known. See for example, U.S. Pat. No. 4,729,376 (Decote, Jr.); U.S.Pat. No. 4,708,142 (Decote, Jr.); U.S. Pat. No. 4,686,988 (Sholder);U.S. Pat. No. 4,969,467 (Callaghan et. al.); and U.S. Pat. No. 5,350,410(Mann et. al.), which patents are hereby incorporated herein byreference. The type of capture detection system used is not critical tothe present invention.

The microcontroller 860 is further coupled to the memory 894 by asuitable data/address bus 896, wherein the programmable operatingparameters used by the microcontroller 860 are stored and modified, asrequired, in order to customize the operation of the implantable device710 to suit the needs of a particular patient. Such operating parametersdefine, for example, pacing pulse amplitude, pulse duration, electrodepolarity, rate, sensitivity, automatic features, arrhythmia detectioncriteria, and the amplitude, wave shape and vector of each shockingpulse to be delivered to the patient's heart 712 within each respectivetier of therapy. The memory 894 can also store data about area under thecurve and/or number of inflection points in a plethysmography signal andbaseline information useful for monitoring for an impending MI.

The operating parameters of the implantable device 710 may benon-invasively programmed into the memory 894 through a telemetrycircuit 801 in telemetric communication with an external device 802,such as a programmer, transtelephonic transceiver, or a diagnosticsystem analyzer. The telemetry circuit 801 can be activated by themicrocontroller 860 by a control signal 806. The telemetry circuit 801advantageously allows intracardiac electrograms and status informationrelating to the operation of the device 710 (as contained in themicrocontroller 860 or memory 894) to be sent to the external device 802through an established communication link 805. The telemetry circuit canalso be use to transmit data relating to a predicted impending MI to theexternal device 802.

For examples of telemetry devices, see U.S. Pat. No. 4,809,697, entitled“Interactive Programming and Diagnostic System for use with ImplantablePacemaker” (Causey, III et al.); U.S. Pat. No. 4,944,299, entitled “HighSpeed Digital Telemetry System for Implantable Device” (Silvian); andU.S. Pat. No. 6,275,734 entitled “Efficient Generation of SensingSignals in an Implantable Medical Device such as a Pacemaker or ICD”(McClure et al.), which patents are hereby incorporated herein byreference.

The implantable device 710 additionally includes a battery 811 whichprovides operating power to all of the circuits shown in FIG. 8. If theimplantable device 710 also employs shocking therapy, the battery 811should be capable of operating at low current drains for long periods oftime, and then be capable of providing high-current pulses (forcapacitor charging) when the patient requires a shock pulse. The battery811 should also have a predictable discharge characteristic so thatelective replacement time can be detected.

The implantable device 710 can also include a magnet detection circuitry(not shown), coupled to the microcontroller 860. It is the purpose ofthe magnet detection circuitry to detect when a magnet is placed overthe implantable device 710, which magnet may be used by a clinician toperform various test functions of the implantable device 710 and/or tosignal the microcontroller 860 that the external programmer 802 is inplace to receive or transmit data to the microcontroller 860 through thetelemetry circuits 801.

As further shown in FIG. 8, the device 710 is also shown as having animpedance measuring circuit 813 which is enabled by the microcontroller860 via a control signal 814. The known uses for an impedance measuringcircuit 813 include, but are not limited to, lead impedance surveillanceduring the acute and chronic phases for proper lead positioning ordislodgement; detecting operable electrodes and automatically switchingto an operable pair if dislodgement occurs; measuring respiration orminute ventilation; measuring thoracic impedance for determining shockthresholds and heart failure condition; detecting when the device hasbeen implanted; measuring stroke volume; and detecting the opening ofheart valves, etc. The impedance measuring circuit 813 is advantageouslycoupled to the switch 874 so that any desired electrode may be used. Theimpedance measuring circuit 813 can be used to obtain an impedanceplethysmography (IPG) signal, which can be used in certain embodimentsof the present invention.

In the case where the implantable device 710 is also intended to operateas an implantable cardioverter/defibrillator (ICD) device, it shoulddetect the occurrence of an arrhythmia, and automatically apply anappropriate electrical shock therapy to the heart aimed at terminatingthe detected arrhythmia. To this end, the microcontroller 860 furthercontrols a shocking circuit 816 by way of a control signal 818. Theshocking circuit 816 generates shocking pulses of low (up to 0.5Joules), moderate (0.5-10 Joules), or high energy (11 to 40 Joules), ascontrolled by the microcontroller 860. Such shocking pulses are appliedto the patient's heart 712 through at least two shocking electrodes, andas shown in this embodiment, selected from the left atrial coilelectrode 728, the RV coil electrode 736, and/or the SVC coil electrode738. As noted above, the housing 740 may act as an active electrode incombination with the RV electrode 736, or as part of a split electricalvector using the SVC coil electrode 738 or the left atrial coilelectrode 728 (i.e., using the RV electrode as a common electrode).

The above described implantable device 710 was described as an exemplarypacing device. One or ordinary skill in the art would understand thatembodiments of the present invention can be used with alternative typesof implantable devices. Accordingly, embodiments of the presentinvention should not be limited to use only with the above describeddevice.

The present invention has been described above with the aid offunctional building blocks illustrating the performance of specifiedfunctions and relationships thereof. The boundaries of these functionalbuilding blocks have often been arbitrarily defined herein for theconvenience of the description. Alternate boundaries can be defined solong as the specified functions and relationships thereof areappropriately performed. Any such alternate boundaries are thus withinthe scope and spirit of the claimed invention. For example, it would bepossible to combine or separate some of the steps shown in the flowdiagrams. Further, it may be possible to change the order of some of thesteps shown in flow diagrams, without substantially changing the overallevents and results. For another example, it is possible to change theboundaries of some of the blocks shown in FIG. 8.

The previous description of the preferred embodiments is provided toenable any person skilled in the art to make or use the embodiments ofthe present invention. While the invention has been particularly shownand described with reference to preferred embodiments thereof, it willbe understood by those skilled in the art that various changes in formand details may be made therein without departing from the spirit andscope of the invention.

What is claimed is:
 1. For use with an implanted system, a method formonitoring for an impending myocardial infarction (MI), the methodcomprising: (a) using an implanted photoplethysmography sensor remotefrom the patient's heart to produce a photoplethysmography signal thatis indicative of changes in arterial volume; (b) for each of a pluralityof periods of time, determining a metric indicative of the area underthe curve of the photoplethysmography signal for the period of time; (c)monitoring for an impending MI based on changes in the metric indicativeof the area under the curve of the photoplethysmography signal; and (d)triggering an alert and/or therapy in response to an impending MI beingdetected at step (c); wherein one or more of steps (b), (c) and (d)is/are performed using a processor.
 2. The method of claim 1, furthercomprising determining a baseline of the metric indicative of area underthe curve; wherein step (c) includes distinguishing between an impendingMI and a transient myocardial ischemic event based on a length of timethat the metric indicative of the area under the curve falls below thebaseline by at least a specified threshold.
 3. The method of claim 1,further comprising determining a baseline of the metric indicative ofarea under the curve; wherein step (c) comprises: (c.1) comparing thedetermined metrics indicative of the area under the curve to thebaseline; and (c.2) predicting an impending MI if the determined metricindicative of the area under the curve falls below the baseline by atleast a specified threshold for at least a specified length of time. 4.The method of claim 3, wherein step (c.2) includes distinguishingbetween an impending MI and a transient myocardial ischemic event basedon a length of time that the metric indicative of the area under thecurve falls below the baseline by at least the specified threshold. 5.The method of claim 1, wherein step (c) comprises predicting animpending MI if a decrease beyond a specified threshold is detected, inthe metric indicative of the area under the curve of thephotoplethysmography signal, from one of the periods of time to theimmediately following one of the periods of time.
 6. The method of claim1, wherein step (c) comprises predicting an impending MI if the metricindicative of the area under the curve of the photoplethysmographysignal decreases by at least a specified amount for at least a specifiedperiod of time.
 7. The method of claim 1, wherein the metric indicativeof area under the curve is selected from the group consisting of: anintegral of at least one cycle of the photoplethysmography signal; awidth from the start to the end of a cycle of the photoplethysmographysignal; and a full width at half maximum (FWHM) of a cycle of thephotoplethysmography signal.
 8. The method of claim 1, wherein step (c)includes: (c.1) detecting changes in the area under the curve of thephotoplethysmography signal that are indicative of changes in vascularstiffness; and (c.2) monitoring for an impending MI based on changes inthe area under the curve of the photoplethysmography signal that areindicative of changes in vascular stiffness.
 9. The method of claim 8,wherein step (c.2) comprises predicting an impending MI if a change inthe area under the curve of the photoplethysmography signal, which isindicative of an increase in vascular stiffness beyond a specifiedthreshold, is detected.
 10. The method of claim 8, wherein step (c.2)comprises predicting an impending MI if a change in the area under thecurve of the photoplethysmography signal, which is indicative of anincrease in vascular stiffness beyond a specified threshold, is detectedwithin a specified time period.
 11. The method of claim 1, wherein themetric indicative of area under the curve, which is determined at step(b) for each of a plurality of periods of time, is indicative of thearea under the curve of at least one entire cycle of thephotoplethysmography signal.
 12. An implantable system for monitoringfor an impending myocardial infarction (MI), comprising: an implantablephotoplethysmography sensor configured to be implanted remote from apatient's heart and to produce a photoplethysmography signal that isindicative of changes in arterial volume; a monitor configured to:determine a metric indicative of the area under the curve of thephotoplethysmography signal for each of a plurality of periods of time,monitor for an impending MI based on changes in the metric indicative ofthe area under the curve of the photoplethysmography signal, and triggeran alert and/or therapy in response to an impending MI being detected.13. The system of claim 12, wherein the monitor is configured to:determine a baseline of the metric indicative of area under the curve;and monitor for an impending MI, based on changes in the metricindicative of the area under the curve of the photoplethysmographysignal, by comparing the determined metrics indicative of the area underthe curve to the baseline, and predicting an impending MI if thedetermined metric indicative of the area under the curve falls below thebaseline by at least a specified threshold for at least a specifiedlength of time.
 14. The system of claim 12, wherein the metricindicative of area under the curve is indicative of the area under thecurve of at least one entire cycle of the photoplethysmography signal.15. For use with a chronically implanted device, a method for monitoringfor an impending myocardial infarction (MI), the method comprising: (a)using an implanted photoplethysmography sensor remote from a patient'sheart to produce a photoplethysmography signal that is indicative ofchanges in arterial volume; (b) for each of a plurality of cycles of thephotoplethysmography signal, determining a metric indicative of a numberof inflections in the photoplethysmography signal for the cycle; (c)monitoring for an impending MI based on changes in the metric indicativeof the number of inflections in the photoplethysmography signal; and (d)triggering an alert and/or therapy in response to an impending MI beingdetected at step (c); wherein one or more of steps (b), (c) and (d)is/are performed using a processor.
 16. The method of claim 15, furthercomprising determining a baseline of the metric of the number ofinflections; wherein step (c) includes distinguishing between animpending MI and a transient myocardial ischemic event based on a lengthof time that the metric indicative of the number of inflectionsincreases beyond the baseline by at least a specified threshold.
 17. Themethod of claim 15, further comprising determining a baseline of themetric indicative of the number of inflections in thephotoplethysmography signal; wherein step (c) comprises: (c.1) comparingthe determined metrics indicative of the number of inflections to thebaseline; and (c.2) predicting an impending MI if the determined metricindicative of the metric indicative of the number of inflectionsincreases beyond the baseline by at least a specified threshold.
 18. Themethod of claim 17, wherein step (c.2) includes distinguishing betweenan impending MI and a transient myocardial ischemic event based on alength of time that the metric indicative of the number of inflectionsremains increased beyond the baseline by at least the specifiedthreshold.
 19. The method of claim 15, wherein step (c) comprisespredicting an impending MI if an increase beyond a specified thresholdis detected, in the metric indicative of the number of inflections inthe photoplethysmography signal, from one of the periods of time to theimmediately following one of the periods of time.
 20. The method ofclaim 15, wherein step (c) comprises predicting an impending MI if themetric indicative of the number of inflections in thephotoplethysmography signal increases by at least a specified amount forat least a specified period of time.
 21. An implantable system formonitoring for an impending myocardial infarction (MI), comprising: animplantable photoplethysmography sensor configured to be implantedremote from a patient's heart and to produce a photoplethysmographysignal that is indicative of changes in arterial volume; a monitorconfigured to determine, for each of a plurality of cycles of thephotoplethysmography signal, a metric indicative of a number ofinflections in the photoplethysmography signal for the cycle, monitorfor an impending MI based on changes in the metric indicative of thenumber of inflections in the photoplethysmography signal, and trigger analert and/or therapy in response to an impending MI being detected. 22.The system of claim 21, wherein the monitor is configured to monitor foran impending MI, based on changes in the metric indicative of the numberof inflections in the photoplethysmography signal, by comparing thedetermined metrics indicative of the number of inflections to abaseline, and predicting an impending MI if the determined metricindicative of the number of inflections increases above the baseline byat least a specified threshold.